In: Clinical Sarcoma Research, 9 (2019), Nr. 2. pp. 1-8. ISSN 2045-3329
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Abstract
Background: Atypical fibroxanthomas (AFX) and pleomorphic dermal sarcomas (PDS) are lesions of the skin with overlapping histologic features and unspecific molecular traits. PDS behaves aggressive compared to AFX. Thus, a precise delineation, although challenging in some instances, is relevant.
Methods: We examined the value of DNA-methylation profiling and copy number analysis for separating these tumors. DNA-methylation data were generated from 17 AFX and 15 PDS using the Illumina EPIC array. These were compared with DNA-methylation data generated from 196 tumors encompassing potential histologic mimics like cutaneous squamous carcinomas (cSCC; n = 19), basal cell carcinomas (n = 10), melanoma metastases originating from the skin (n = 11), leiomyosarcomas (n = 11), angiosarcomas of the skin and soft tissue (n = 11), malignant peripheral nerve sheath tumors (n = 19), dermatofibrosarcomas protuberans (n = 13), extraskeletal myxoid chondrosarcomas (n = 9), myxoid liposarcomas (n = 14), schwannomas (n = 10), neurofibromas (n = 21), alveolar (n = 19) and embryonal (n = 17) rhabdomyosarcomas as well as undifferentiated pleomorphic sarcomas (n = 12).
Results: DNA-methylation profiling did not separate AFX from PDS. The DNA-methylation profiles of the other cases, however, were distinct from AFX/PDS. They reliably assigned to subtype-specific DNA-methylation clusters, although overlap occurred between some AFX/PDS and cSCC. Copy number profiling revealed alterations in a similar frequency and distribution between AFX and PDS. They involved losses of 9p (22/32) and 13q (25/32). Gains frequently involved 8q (8/32). Notably, a homozygous deletion of CDKN2A was more frequent in PDS (6/15) than in AFX (2/17), whereas amplifications were non-recurrent and overall rare (5/32).
Conclusions: Our findings support the concept that AFX and PDS belong to a common tumor spectrum. We could demonstrate the diagnostic value of DNA-methylation profiling to delineating AFX/PDS from potential mimics. However, the assessment of certain histologic features remains crucial for separating PDS from AFX.
Document type: | Article |
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Journal or Publication Title: | Clinical Sarcoma Research |
Volume: | 9 |
Number: | 2 |
Publisher: | BioMed Central |
Place of Publication: | London |
Date Deposited: | 05 Apr 2019 12:49 |
Date: | 2019 |
ISSN: | 2045-3329 |
Page Range: | pp. 1-8 |
Faculties / Institutes: | Service facilities > German Cancer Research Center (DKFZ) Medizinische Fakultät Heidelberg > Institut für Immunologie Medizinische Fakultät Heidelberg > Pathologisches Institut |
Uncontrolled Keywords: | Pleomorphic dermal sarcoma, Atypical fibroxanthoma, Sarcomas, Melanomas, Carcinomas, Mimics, DNA methylation, Profiling |